Growing incidence of HPV-positive oropharyngeal cancer in HK

A retrospective study by the Chinese University of Hong Kong (CUHK) reports a growing incidence of oropharyngeal cancer, with an increasing proportion of human papillomavirus (HPV)–positive cases in Hong Kong in recent years.

Oropharyngeal cancer is a subtype of head and neck cancer, which can be caused by tobacco, alcohol and pollutants or high-risk types of HPV. [Cancer 1993;72:1369-1375; J Natl Cancer Inst 2000;92:709-720] Reports published over the last decade indicate an increasing burden of oropharyngeal squamous cell carcinoma (SCC) in Europe, North America, Australia, and New Zealand. [Cancer Epidemiol Biomark Prev 2022;31:2054-2062; J Surg Oncol 2021;124:920-922] As Hong Kong–specific data were scarce, the CUHK researchers set out to investigate local temporal trends in oropharyngeal SCC and HPV prevalence to inform public health policy. [Jpn J Clin Oncol 2018;1:13-21]

The incidence of site-specific head and neck cancers was determined on the basis of territory-wide cancer statistics captured by the Hong Kong Cancer Registry between 1986 and 2020, while the proportion of HPV-positive cases was estimated by testing tissue samples from patients diagnosed with oropharyngeal SCC between 2010 and 2020 at four major hospitals in Hong Kong. [Cancers (Basel) 2024;16:226]

The 5-year average annual age-standardized incidence rates of nasopharyngeal and laryngeal cancers declined markedly from 18.5 cases and 6.6 cases per 100,000 people in 1986–1990 to 6.6 cases and 1.2 cases per 100,000 people in 2016–2020, respectively, but no such trend was observed for cancers of the oropharynx and oral cavity during the same period.

Tobacco is a common risk factor for both oropharyngeal and laryngeal cancers, yet only oropharyngeal cancer has a strong aetiological association with HPV. Comparing the incidence of laryngeal and oropharyngeal SCC, the researchers found that while the annual number of new laryngeal SCC cases had decreased from 300 in 1986 to 162 in 2020, that of oropharyngeal SCC had increased from 36 cases to 116 cases over the same period.

“The opposite incidence trends of these two cancers suggest that HPV is the driving force for the consistent increase in incidence of oropharyngeal cancer over the last few decades in Hong Kong. Given the strong carcinogenicity of HPV, tobacco control alone is unlikely to be sufficient for combating oropharyngeal cancer,” remarked the researchers.

Further analysis of 310 oropharyngeal SCC cases diagnosed between 2010 and 2020, which had adequate DNA quality in the tumour samples, showed that 112 (36.0 percent) were positive for high-risk types of HPV (eg, HPV16, HPV58 and HPV33). Of note, the high-risk HPV positivity rate of oropharyngeal SCC was significantly higher for cases diagnosed in 2016–2020 vs those diagnosed in 2010–2015 (41.9 percent vs 28.2 percent; p=0.006). While the majority of patients with oropharyngeal SCC were men (82.6 percent), rates of high-risk HPV in the tumour samples were similar between men (36.3 percent) and women (35.2 percent).

The high-risk HPV positivity rate was particularly high for tonsil (56.1 percent) vs nontonsil (21.3 percent) oropharyngeal SCC. The proportion of HPV-positive tonsil SCC had also significantly increased in recent years, from 40.4 percent in 2010–2015 to 64.7 percent in 2016–2020 (p=0.007). Notably, patients with HPV-positive tonsil cancer were significantly younger than HPV-negative cases (mean age, 58.9 years vs 64.3 years; p=0.006).

“While Hong Kong’s current number of approximately 100 new cases of oropharyngeal cancer per year is relatively low, action should be taken early to prevent a further upsurge in the coming decades. A gender-neutral HPV vaccination programme in Hong Kong is worth considering,” advised the researchers.
 
Additional insights
MIMS Doctor spoke to the study’s corresponding author, Professor Paul Chan of Department of Microbiology at CUHK, to gain additional insights.

MIMS Doctor: What are the main findings of your recent study on changes in the incidence of human papillomavirus HPV-positive oropharyngeal SCC in Hong Kong?

Prof Chan: We noted a consistent increase in oropharyngeal cases of SCC, in particular, tonsil subtype, over the last 15 years in Hong Kong, which was driven by oral infection with high-risk HPV subtypes.

MIMS Doctor: What do you think is driving the growing incidence of HPV-positive oropharyngeal cancer in Hong Kong?

Prof Chan: A study conducted locally a few years ago, which was aimed at identifying risk factors driving HPV-positive oropharyngeal cancers, showed that HPV-positive cases were associated with smoking, alcohol drinking, multiple sexual partners, and oral sex. Changes in some of these lifestyle aspects over the past decade have increased the risk of oral HPV infection, which can lead to the development of oropharyngeal cancer in a proportion of infected individuals.

MIMS Doctor: What is the significance of the finding that patients with HPV-positive tonsil cancer were significantly younger than HPV-negative cases?

Prof Chan: Many members of the public may think that cancer primarily affects older people and that younger individuals are not at risk. Our data provides evidence for alerting younger people and medical professionals to the possibility of oropharyngeal cancer at relatively young age. Raising awareness is important for early detection, as it can improve prognosis.

Currently, oropharyngeal cancer patients tend to be diagnosed at quite a late stage, as the symptoms, such as a sore throat and hoarse voice, can be unspecific and regarded as trivial. The increasing trend in the incidence of oropharyngeal cancers should make healthcare professionals more alert to these symptoms being potentially indicative of this type of cancer and help them initiate further investigation. 

MIMS Doctor: Is HPV-positivity rate similar between male and female cases of oropharyngeal SCC?

Prof Chan: Oropharyngeal and tonsil cancer is more common in men. However, HPV-positivity rate of oropharyngeal and tonsil cancer is roughly the same for male and female cases.

MIMS Doctor: Is there a growing awareness of HPV’s association with other cancers apart from cervical cancer, in particular, oropharyngeal cancer? What more can be done to enhance this awareness among healthcare professionals, policy makers and the general public?

Prof Chan: Awareness of HPV-positive cancers affecting sites other than the cervix is improving in the West. However, awareness of non-cervical HPV-positive cancers is still lagging behind in Asia, including Hong Kong. Hopefully, our data can help improve it.

MIMS Doctor: What are the implications of your study to public health policy? What could be done to reverse the growing incidence of oropharyngeal cancer in Hong Kong?

Prof Chan: Our study has documented an increase in the number of oropharyngeal cancers and showed that this increase was driven by an increase in oral HPV infections. To minimize the risk of oropharyngeal cancer, we advocate no smoking, less drinking, and importantly, minimization of oral HPV infections. The latter can be achieved through education, including safe sex, and through vaccination, which increases protection against HPV infection, including in the oral cavity. Education needs to take place both at individual level, so as to enhance vaccine acceptance, and among policy makers who may consider expanding the vaccination programme [from girls alone] to boys as well.

As a future research direction, development of a screening tool, perhaps similar to Pap smears, would enhance early detection of oropharyngeal cancer. Currently, there isn’t a good screening test for oropharyngeal cancer [anywhere in the world].